Kaweme Natasha Mupeta, Zhou Shu, Changwe Geoffrey Joseph, Zhou Fuling
Department of Hematology, Zhongnan Hospital affiliated to Wuhan University, No. 169 Donghu road, 430071, Wuhan, P.R. China.
School of Medicine, Shandong University, No. 44, Wenhua West Road, Jinan, 250012, P.R. China.
Biomark Res. 2020 Nov 11;8(1):63. doi: 10.1186/s40364-020-00242-z.
Excessive generation of reactive oxygen species (ROS) in the presence of a defective antioxidant system can induce cellular damage and disrupt normal physiological functions. Several studies have revealed the unfavorable role of ROS in promoting the growth, proliferation, migration, and survival of leukemia cells. In this review study, we summarize the mechanisms of ROS production and its role in leukemogenesis, counteractive effects of antioxidants, and implicate the current ROS-dependent anticancer therapies in acute myeloid leukemia. BODY: The dysregulation of the redox system is known to play a significant role in the pathogenesis of leukemia. Leukemia cells generate high levels of ROS, which further increases the levels through extra pathways, including mitochondrial deoxyribonucleic mutation, leukemic oncogene activation, increased nicotinamide adenine phosphate hydrogen (NADPH), and cytochrome P450 activities. Aforementioned pathways once activated have shown to promote genomic instability, induce drug resistance to leukemia medical therapy, disease relapse and reduce survival period. The current standard of treatment with chemotherapy employs the pro-oxidant approach to induce apoptosis and promote tumor regression. However, this approach retains several deleterious effects on the subject resulting in degradation of the quality of life. Nevertheless, the addition of an antioxidant as an adjuvant drug to chemotherapy alleviates treatment-related toxicity, increases chemotherapeutic efficacy, and improves survival rates of a patient.
Acute myeloid leukemia remains a daunting challenge to clinicians. The desire to achieve the maximum benefit of chemotherapy but also improve patient outcomes is investigated. ROS generated through several pathways promotes leukemogenesis, drug resistance, and disease relapse. Chemotherapy, the mainstay of treatment, further upregulates ROS levels. Therefore, the addition of an antioxidant to leukemia medical therapy alleviates toxicity and improves patient outcomes.
在抗氧化系统存在缺陷的情况下，活性氧（ROS）过度生成会导致细胞损伤并破坏正常生理功能。多项研究揭示了ROS在促进白血病细胞生长、增殖、迁移和存活方面的不利作用。在本综述研究中，我们总结了ROS产生的机制及其在白血病发生中的作用、抗氧化剂的对抗作用，并探讨了当前急性髓系白血病中依赖ROS的抗癌疗法。
氧化还原系统失调在白血病发病机制中起着重要作用。白血病细胞产生高水平的ROS，通过包括线粒体脱氧核糖核酸突变、白血病癌基因激活、烟酰胺腺嘌呤磷酸氢（NADPH）增加和细胞色素P450活性等额外途径进一步提高其水平。上述途径一旦被激活，已显示会促进基因组不稳定、诱导对白血病药物治疗的耐药性、疾病复发并缩短生存期。目前化疗的标准治疗方法采用促氧化方法诱导细胞凋亡并促进肿瘤消退。然而，这种方法对患者仍有一些有害影响，导致生活质量下降。尽管如此，在化疗中添加抗氧化剂作为辅助药物可减轻治疗相关毒性、提高化疗疗效并改善患者生存率。
急性髓系白血病对临床医生来说仍然是一项艰巨的挑战。人们正在研究如何在实现化疗最大益处的同时改善患者预后。通过多种途径产生的ROS促进白血病发生、耐药性和疾病复发。作为主要治疗手段的化疗会进一步上调ROS水平。因此，在白血病治疗中添加抗氧化剂可减轻毒性并改善患者预后。
